期刊
CELL STEM CELL
卷 5, 期 1, 页码 64-75出版社
CELL PRESS
DOI: 10.1016/j.stem.2009.04.003
关键词
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资金
- American Cancer Society [RSG-07-082-01-MGO]
- Susan G. Komen Foundation [BCTR600208]
- Leukemia and Lymphoma Society/Hildegarde D. Becher Foundation
- NCI Cancer Center [CA-16672]
- Anderson Cancer Center
- Canadian Institutes of Health Research [MOP-64211]
- Rita Allen Foundation
- V Foundation for Cancer Research
The cellular mechanisms that regulate the maintenance of adult tissue stem cells are still largely unknown. We show here that the p53 family member, TAp63, is essential for maintenance of epidermal and dermal precursors and that, in its absence, these precursors senesce and skin ages prematurely. Specifically, we have developed a TAp63 conditional knockout mouse and used it to ablate TAp63 in the germline (TAp63(-/-)) or in K14-expressing cells in the basal layer of the epidermis (TAp63(fl/fl) ;K14cre+). TAp63(-/-) mice age prematurely and develop blisters, skin ulcerations, senescence of hair follicle-associated dermal and epidermal cells, and decreased hair morphogenesis. These phenotypes are likely due to loss of TAp63 in dermal and epidermal precursors since both cell types show defective proliferation, early senescence, and genomic instability. These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging.
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